Tumor Microenvironment-Selective Sol–Gel Mineralization of ROS-Responsive Stretchable and Conductive Hydrogel,Advanced Functional Materials

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Tumor Microenvironment-Selective Sol–Gel Mineralization of ROS-Responsive Stretchable and Conductive Hydrogel
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2024-04-11 , DOI: 10.1002/adfm.202402367
Akhmad Irhas Robby _{1,

2} , Jun‐Ho Yang ₃ , Eun‐Jung Jin _{3,

4} , Sung Young Park _{1,

2,

5}

Affiliation

Cancer cell-triggered sol–gel transformation of mineralized hydrogel (PAA-MnO₂) is designed as a facile strategy for cancer detection by manipulating the mineralization process in the presence of cancer cells. The mineralization of polyacrylic acid (PAA) with calcium phosphate via carboxyl-Ca²⁺ complex is initially inhibited by the incorporation of reactive oxygen species (ROS)-sensitive manganese oxide (MnO₂) with polymer dots (PDs). In this system, the mineralization can be induced after cleaving MnO₂ into Mn²⁺ by high ROS levels in cancer cells, forming a PAA-MnO₂ mineralized hydrogel and resulting in a naked-eye system for cancer monitoring. Naked-eye monitoring of ROS-responsive sol–gel transformation is performed using a circulator device containing circulating cells to discriminate cancer (HeLa, PC-3, B16F10) from normal cells (CHO-K1). With the incorporation of PDs, PAA-MnO₂ mineralized hydrogel not only provides physical transformation (stretchability, viscosity) but also fluorescence-recovery and electroconductivity changes at different cancer-cell concentrations (10⁴–10⁶ cells mL⁻¹), including distinct strain–pressure responses that can be wirelessly monitored via smartphones. Furthermore, in vivo, experiments suggest that PAA-MnO₂ mineralized hydrogel can be formed in tumor-bearing mice owing to its excellent ROS-scavenging activity at the tumor site, as confirmed by SOD2 and gene-expression analysis. Thus, this unique approach can potentially enable simple and effective cancer detection in future point-of-care diagnostics.

中文翻译：

ROS响应性可拉伸导电水凝胶的肿瘤微环境选择性溶胶-凝胶矿化

癌细胞触发矿化水凝胶（PAA-MnO ₂ ）的溶胶-凝胶转化被设计为通过在癌细胞存在的情况下操纵矿化过程来检测癌症的简便策略。聚丙烯酸（PAA）与磷酸钙通过羧基-Ca ²⁺络合物的矿化最初通过将活性氧（ROS）敏感的氧化锰（MnO ₂ ）与聚合物点（PD）结合来抑制。在该系统中，癌细胞中高ROS水平将MnO ₂裂解成Mn ²⁺后可诱导矿化，形成PAA-MnO ₂矿化水凝胶，从而形成用于癌症监测的裸眼系统。使用含有循环细胞的循环器装置对 ROS 响应溶胶-凝胶转化进行肉眼监测，以区分癌症（HeLa、PC-3、B16F10）和正常细胞（CHO-K1）。通过掺入PD，PAA-MnO ₂矿化水凝胶不仅提供物理转变（拉伸性、粘度），而且在不同癌细胞浓度（10 ⁴ –10 ⁶ cells mL ^-1 ）下提供荧光恢复和电导率变化，包括不同的可以通过智能手机无线监控应变-压力响应。此外，在体内实验表明，PAA-MnO ₂矿化水凝胶可以在荷瘤小鼠中形成，因为它在肿瘤部位具有出色的ROS清除活性，SOD2和基因表达分析证实了这一点。因此，这种独特的方法有可能在未来的护理诊断中实现简单有效的癌症检测。

更新日期：2024-04-11

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